Thalassemia major is a genetically transmitted catastrophic illness that, with best available therapy, rarely allows survivors beyond the second or third decade of life. Two recent reports from bone marrow transplant centers in Seattle and in Pesearo, Italy, as well as data submitted to the International Bone Marrow Transplant Registry (IBMTR) suggest that marrow allografts may results in cures. In the proposed research, the Advisory Committee of the IBMTR will investigate the efficacy of bone marrow transplantation as a cure for thalassemia major. As is the case with severe aplastic anemia, graft failure/rejection has been a major cause of treatment failure for the limited number of marrow allografts for thalassemia major reported thus far in the scientific literature; 8 of 15 patients reported (53%) did not obtain stable engraftment of donor hematopoietic stem cells. Detailed data for 22 allografted thalassemia patients have been reported to the IBMTR and 17 of these cases were reported in 1983. Based upon the recent rapid growth in the field of bone marrow transplantation, participation in the IBMTR program by 90 active bone marrow transplant centers worldwide, and the surge of interest in the application of bone marrow transplantation for thalassemia major, we estimate that data for more than 100 patients will be available for the proposed research. Multivariate statistical methods which take into account and adjust for interactions between variables will be employed to evaluate more than 30 prognostic variables that may influence survival and stable engraftment. Additional studies will be performed to investigate possible associations between HLA antigens and thalassemia major and to determine whether the parents of thalassemia major patients have increased sharing of HLA antigens in comparison with the parents of healthy children.